title: Aging-related changes in RP3V kisspeptin neurons predate the reduced activation of GnRH neurons during the early reproductive decline in female mice.
abstract: Kisspeptin neurons in the rostral periventricular area of the third ventricle (RP3V) play a key role in relaying the positive feedback effects of estradiol that activate gonadotropin-releasing hormone (GnRH) neurons and drive a surge in the GnRH/luteinizing hormone (LH) level. However, the precise role of kisspeptin neurons during female reproductive senescence remains unclear. Focusing on middle-aged intact female mice with irregular estrous cycles, we found a parallel decline in c-Fos-positive kisspeptin neurons and c-Fos-positive GnRH neurons at the time of the GnRH/LH surge. Furthermore, in kisspeptin neurons, the expression of estrogen receptor α (ERα), but not progesterone receptor (PR), decreased with age. Interestingly, some kisspeptin neurons in the RP3V, but none of the GnRH neurons in the rostral preoptic area (rPOA), had a characteristic cellular senescence in middle-aged mice and old mice. These data suggest that, among the groups of neurons involved in reproductive control, the kisspeptin neurons in the RP3V are likely among the earliest to undergo aging processes and thus participate in initiating the early reproductive decline.
authors.affiliation: Key Laboratory of Brain Aging and Neurodegenerative Disease, Fujian Institute of Geriatrics, The Affiliated Union Hospital of Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Molecular Neurology, Fujian Medical University, Fuzhou, China. Electronic address: drzj@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Lumeng
authors.initials: L
authors.lastname: Yang
authors.forename: Nan
authors.initials: N
authors.lastname: Lin
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Pan
authors.forename: Yuangui
authors.initials: Y
authors.lastname: Zhu
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Chen
mesh_terms: D000375:Aging / Q000235:genetics* / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000166:cytology* / Q000378:metabolism / Q000473:pathology*; D047628:Estrogen Receptor alpha; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism / Q000502:physiology*; D007150:Immunohistochemistry; D059648:Kisspeptins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos; D011980:Receptors, Progesterone; D012098:Reproduction / Q000235:genetics* / Q000502:physiology*
chemical_list: D047628:Estrogen Receptor alpha; D059648:Kisspeptins; D016760:Proto-Oncogene Proteins c-fos; D011980:Receptors, Progesterone; D007987:Gonadotropin-Releasing Hormone
keywords: Aging; Estrogen receptor–α; GnRH; Kisspeptin; Progesterone receptor; c-Fos